The aim of this research is to develop a new myocardial imaging agent. Despite the physiological importance of norepinephrine as an adrenergic transmitter, no radiopharmaceutical exists that can assess catecholamine hormone accumulation and turnover in peripheral tissue. This proposal focuses on radiolabeled analogs of guanethidine, a drug that shares certain storage characteristics with norepinephrine. Radiopharmaceutical analogs could serve to simplify the complex disposition of norepinephrine by mimicking only a few, but nonetheless important, determinants of its in vivo distribution. The adrenergic physiology of the normal and diseased heart could be probed non-invasively by established Nuclear Cardiology techniques. The following methods will be used: 1. A structure-distribution study of twenty-five I-125 iodoaralkylguanidine analogs will be performed. 2. The I-125 compounds showing the highest myocardial and neuronal specificity will be I-123 or I-131 labeled for planar and tomographic imaging evaluation in dogs and monkeys. 3. F-18 labeled fluoromethylbenzylguanidines will be evaluated as possible positron-emitting imaging agents for the heart. 4. The mechanism of localization of these agents will be determined by: regional heart distribution studies, nerve isolation, and comparison with exogenous and endogenous levels of norepinephrine. The ultimate goal is to develop both single photon and positron-emitting heart agents that will provide functional information on the sympathetic tone of the heart, especially in diseases such as heart failure which displays altered norepinephrine binding capacity.